Method and apparatus for treatment of intracranial hemorrhages

ABSTRACT

An ultrasound catheter with a lumen for fluid delivery and fluid evacuation, and an ultrasound source is used for the treatment of intracerebral or intraventricular hemorrhages. After the catheter is inserted into a blood clot, a lytic drug can be delivered to the blood clot via the lumen while applying ultrasonic energy to the treatment site. As the blood clot is dissolved, the liquefied blood clot can be removed by evacuation through the lumen.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the priority benefit of U.S. ProvisionalApplication No. 61/377,639, filed Aug. 27, 2010, the entire contents ofwhich is hereby incorporated by reference herein.

STATEMENT REGARDING FEDERALLY SPONSORED R&D

The invention was made with government support under Grant No.1RC3NS070623-01 awarded by the National Institutes of Health and theNational Institute of Neurological Disorders and Stroke. The governmenthas certain rights to the invention.

BACKGROUND OF THE INVENTION

Field of the Invention

The present invention relates to methods and apparatuses for thetreatment of intracranial hemorrhages, and more specifically, to methodsand apparatuses for the treatment of intracranial hemorrhages using anultrasound.

Background of the Invention

A large number of Americans each year suffer a hemorrhagic stroke. Mostof these occur in the basal ganglia, and a third of those includebleeding into the ventricles. Half of these victims will die withinmonths, and a quarter of the survivors will have a second stroke withinfive years. Bleeding in the brain occurs due to high blood pressure,aneurysms, and less frequently arterio-venous malformations (AVM), andincreases in incidence with age. Factors including smoking, diabetes,and obesity play roles, as do amyloid deposits in the elderly.

With respect to stroke treatment, up to a large number of cases per yearinvolve surgical intervention. The objectives of surgical interventiongenerally include clipping bleeding aneurysms, removing bleeding AVMs,and removing clot volume in intracranial hemorrhages (ICH).

In certain applications, an interventional radiologist will insertGoldvalve detachable balloons, Guglielmi detachable coils, or Onyxliquid embolic to occlude AVMs and saccular aneurysm. These applicationsare primarily preventive (e.g., preventing a second bleed). Othermethods of reducing further bleeding include using embolics and FVIIa,and/or maintaining intracranial pressure below mean arterial pressure.Medical therapy typically also includes head elevation, Tylenol fortemperature reduction, paralytics to prevent coughing, intubation toprevent aspiration, Mannitol and diuretics to reduce fluid volume, andseizure preventatives.

Recently, lytics have been considered as a treatment option to removeobstruction in the ventricles and to reduce intracranial pressure. Seee.g., U.S. Patent Publication No. 2006/0078555 to Hanely et al.published on Apr. 13, 2006 and filed on Mar. 29, 2003. However, suchtreatment has not been widely adopted because it is generally consideredtoo slow to provide sufficient clinical benefits. More recently,therapies have been developed that combine ultrasound with a lytic suchas recombinant tissue plasminogen activator (rt-PA). In such therapies,the lytic and ultrasound can delivered through a microcatheter directlyinto spontaneous IVH or ICH patients, to facilitate evacuation of thehemorrhage. See e.g., U.S. Patent Publication No. 2008/0319376 to Wilcoxet al. published on Dec. 25, 2008 and filed on Jun. 20, 2008.

While such therapies have shown promise, there is a general desire tocontinue to improve the methods and apparatuses involved with suchtherapy.

SUMMARY OF THE INVENTIONS

An embodiment of an ultrasound catheter for treatment of a blood clotresulting from an intracranial hemorrhage comprises an elongate tubularbody having a distal portion, a proximal portion, and a central lumen.The catheter further comprises a plurality of ultrasound radiatingelements positioned within the tubular body. A plurality of ports arelocated on the distal portion of the elongate tubular body, and areconfigured to allow a fluid to flow through the ports.

In another embodiment an ultrasound catheter assembly includes anelongate tubular body having a distal portion and a proximal portion.The elongate tubular body has material properties similar to that ofstandard external ventricular drainage (EVD) catheter. A lumen is formedwithin the elongate tubular body. The lumen includes a plurality ofports on the distal portion of the elongate tubular body configured toallow fluid to flow therethrough. An ultrasonic core is configured to bereceived within the lumen of the catheter. The ultrasonic core comprisesa plurality of ultrasound radiating elements.

In another embodiment, an ultrasound catheter comprises an elongatetubular body having a distal portion and a proximal portion. A firstdrainage lumen is formed within the elongate tubular body. The drainagelumen includes a plurality of drainage ports on the distal portion ofthe elongate tubular body configured to allow fluid to flowtherethrough. A delivery lumen is formed within the elongate tubularbody. The delivery lumen includes a plurality of delivery ports on thedistal portion of the elongate tubular body configured to allow fluid toflow therethrough. A plurality of ultrasound radiating elements arepositioned within the elongate tubular body.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments of the method and apparatus for treatment ofintracranial hemorrhages are illustrated in the accompanying drawings,which are for illustrative purposes only. The drawings comprise thefollowing figures, in which like numerals indicate like parts.

FIG. 1A is a schematic illustration of an ultrasonic catheter configuredfor insertion within the cranial cavity.

FIG. 1B is an enlarged detail view of the distal end of the ultrasoniccatheter shown in FIG. 1A.

FIG. 1C is an enlarged detail view of the proximal end of the ultrasoniccatheter shown in FIG. 1A.

FIG. 1D is a schematic illustration of a stylet that can inserted intothe ultrasonic catheter shown in FIG. 1A.

FIG. 1E is a schematic illustration of ultrasonic core that can insertedinto the ultrasonic catheter shown in FIG. 1A.

FIG. 1F is cross-sectional view taken through line 1F-1F of FIG. 1A.

FIG. 1G is a cross-sectional view of an ultrasonic catheter, accordingto an embodiment.

FIG. 1H is a cross-sectional view of an ultrasonic catheter, accordingto another embodiment.

FIG. 2A is a schematic illustration of an ultrasonic catheter withembedded wires.

FIG. 2B is an enlarged detail view of the distal end of the ultrasoniccatheter shown in FIG. 2A.

FIG. 2C is an enlarged detail view of a medial portion of the ultrasoniccatheter shown in FIG. 2A.

FIG. 2D is an enlarged detail view of the proximal end of the ultrasoniccatheter shown in FIG. 2A.

FIG. 3 is a schematic illustration of an ultrasonic catheter partiallyinserted into the brain.

FIG. 4A is a schematic illustration of an ultrasonic catheter configuredfor insertion within the cranial cavity.

FIG. 4B is a cross-sectional of the ultrasonic catheter shown in FIG.4A.

FIG. 5A is a schematic illustration of an ultrasonic catheter configuredfor insertion within the cranial cavity, according to yet anotherembodiment

FIG. 5B is a cross-sectional view taken of the ultrasonic catheter shownin FIG. 5A.

FIG. 6A is a perspective view of a feature for receiving an ultrasonicelement.

FIG. 6B is a perspective view of another embodiment of a feature forreceiving an ultrasonic element.

FIG. 7A is a schematic illustration of an ultrasonic catheter with acoaxial drain port.

FIG. 7B is an axial view of the ultrasonic catheter shown in FIG. 7A.

FIG. 7C is a perspective view of the ultrasonic catheter of FIG. 7A.

FIG. 8A is a schematic illustration of an ultrasonic catheter with drainports proximal to the connector.

FIG. 8B is a perspective view of the ultrasonic catheter of FIG. 8A.

FIG. 9A is an exploded view of an ultrasonic catheter, according to anembodiment.

FIG. 9B is a schematic illustration of the ultrasonic catheter shown inFIG. 9A.

FIG. 9C is a cross-sectional view of the tubular body of the ultrasoniccatheter shown in FIG. 9B.

FIG. 9D is an enlarged detail view of the distal end of the ultrasoniccatheter shown in FIG. 9B.

FIG. 9E is a cross-sectional view of the distal extrusion of theultrasonic catheter shown in FIG. 9D.

FIG. 9F is a perspective view of the ultrasonic catheter shown in FIG.9B

FIG. 10A is an exploded view of an ultrasonic catheter, according toanother embodiment.

FIG. 10B is a schematic illustration of the ultrasonic catheter shown inFIG. 10A.

FIG. 10C is a cross-sectional view of the ultrasonic catheter shown inFIG. 10B.

FIG. 10D is a perspective view of the spiral extrusion shown in FIG.10A.

FIG. 11A is a schematic view of a drain, according to one embodiment.

FIG. 11B is a cross-sectional view of the drain shown in FIG. 11A.

FIG. 11C is a perspective view of the drain shown in FIG. 11A.

FIG. 11D is a schematic view of an ultrasonic core, according to oneembodiment.

FIG. 11E is a perspective view of the ultrasonic core shown in FIG. 11D.

FIG. 11F is a perspective view of a catheter assembly, according to oneembodiment.

FIG. 11G is a schematic view of the catheter assembly shown in FIG. 11F.

FIG. 11H is an enlarged detail view of the distal end of the drain shownin FIG. 11A.

FIG. 11I is an enlarged detail view of the distal end of the ultrasoniccore shown in FIG. 11D.

FIG. 12A is a schematic view of an ultrasonic core wire, according toone embodiment.

FIG. 12B is a perspective view of an ultrasonic core wire withultrasonic transducers affixed thereto.

FIG. 12C is a perspective view of an ultrasonic core wire with apolyimide shell surrounding ultrasonic transducers.

FIG. 13 is a schematic illustration of an ultrasonic element within afluid-filled chamber, according to one embodiment.

FIG. 14 is a block diagram of a feedback control system for use with anultrasonic catheter.

FIG. 15 is a table listing certain features of various embodiments of anultrasonic catheter.

FIG. 16A is a perspective view of an ultrasonic catheter, according toanother embodiment.

FIGS. 16B-D are enlarged detail views of the distal portion of theultrasonic catheter shown in FIG. 16A. is a schematic illustration ofthe ultrasonic catheter shown in FIG. 10A.

FIG. 16E is a schematic illustration of wires and ultrasonic radiatingmembers embedded within the ultrasonic catheter shown in FIG. 16A.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

As set forth above, methods and apparatuses have been developed thatallow an intracranial hemorrhage and/or a subarachnoid hemorrhage to betreated using ultrasonic energy in conjunction with a therapeuticcompound. As used herein, the term “intracranial hemorrhage” encompassesboth intracerebral hemorrhage and intraventricular hemorrhage. Althoughsome embodiments may be disclosed with reference to intracerebralhemorrhage or intraventricular hemorrhage, the embodiments can generallybe used to treat both types of intracranial hemorrhages. Disclosedherein are several exemplary embodiments of ultrasonic catheters thatcan be used to enhance the efficacy of therapeutic compounds at atreatment site within a patient's body. Also disclosed are exemplarymethods for using such catheters. For example, as discussed in greaterdetail below, the ultrasonic catheters disclosed herein can be used todeliver a therapeutic compound to a blood clot in the brain, allowing atleast a portion of the blood clot to be dissolved and/or removed,thereby reducing damage to brain tissue. Although described with respectto intracranial use, the embodiments disclosed herein are also suitablefor intraventricular use in other applications. Accordingly, the term“intracranial use” can also include intraventricular use.

As used herein, the term “therapeutic compound” refers broadly, withoutlimitation, and in addition to its ordinary meaning, to a drug,medicament, dissolution compound, genetic material or any othersubstance capable of effecting physiological functions. Additionally, amixture including substances such as these is also encompassed withinthis definition of “therapeutic compound”. Examples of therapeuticcompounds include thrombolytic compounds, anti-thrombosis compounds, andother compounds used in the treatment of vascular occlusions and/orblood clots, including compounds intended to prevent or reduce clotformation, neuroprotective agents, anti-apoptotic agents, and neurotoxinscavenging agents. Exemplary therapeutic compounds include, but are notlimited to, heparin, urokinase, streptokinase, tPA, rtPA, BB-10153(manufactured by British Biotech, Oxford, UK), plasmin, IIbIIainhibitors, desmoteplase, caffeinol, deferoxamine, and factor VIIa.

As used herein, the terms “ultrasonic energy”, “ultrasound” and“ultrasonic” refer broadly, without limitation, and in addition to theirordinary meaning, to mechanical energy transferred through longitudinalpressure or compression waves. Ultrasonic energy can be emitted ascontinuous or pulsed waves, depending on the parameters of a particularapplication. Additionally, ultrasonic energy can be emitted in waveformshaving various shapes, such as sinusoidal waves, triangle waves, squarewaves, or other wave forms. Ultrasonic energy includes sound waves. Incertain embodiments, the ultrasonic energy referred to herein has afrequency between about 20 kHz and about 20 MHz. For example, in oneembodiment, the ultrasonic energy has a frequency between about 500 kHzand about 20 MHz. In another embodiment, the ultrasonic energy has afrequency between about 1 MHz and about 3 MHz. In yet anotherembodiment, the ultrasonic energy has a frequency of about 2 MHz. Incertain embodiments described herein, the average acoustic power of theultrasonic energy is between about 0.01 watts and 300 watts. In oneembodiment, the average acoustic power is about 15 watts.

As used herein, the term “ultrasound radiating element” or “ultrasoundor ultrasonic element” refers broadly, without limitation, and inaddition to its ordinary meaning, to any apparatus capable of producingultrasonic energy. An ultrasonic transducer, which converts electricalenergy into ultrasonic energy, is an example of an ultrasound radiatingelement. An exemplary ultrasonic transducer capable of generatingultrasonic energy from electrical energy is a piezoelectric ceramicoscillator. Piezoelectric ceramics typically comprise a crystallinematerial, such as quartz, that changes shape when an electrical currentis applied to the material. This change in shape, made oscillatory by anoscillating driving signal, creates ultrasonic sound waves. In otherembodiments, ultrasonic energy can be generated by an ultrasonictransducer that is remote from the ultrasound radiating element, and theultrasonic energy can be transmitted, via, for example, a wire that iscoupled to the ultrasound radiating element. In such embodiments, a“transverse wave” can be generated along the wire. As used herein is awave propagated along the wire in which the direction of the disturbanceat each point of the medium is perpendicular to the wave vector. Someembodiments, such as embodiments incorporating a wire coupled to anultrasound radiating element for example, are capable of generatingtransverse waves. See e.g., U.S. Pat. Nos. 6,866,670, 6,660,013 and6,652,547, the entirety of which are hereby incorporated by referenceherein. Other embodiments without the wire can also generate transversewaves along the body of the catheter.

In certain applications, the ultrasonic energy itself provides atherapeutic effect to the patient. Examples of such therapeutic effectsinclude blood clot disruption; promoting temporary or permanentphysiological changes in intracellular or intercellular structures; andrupturing micro-balloons or micro-bubbles for therapeutic compounddelivery. Further information about such methods can be found in U.S.Pat. Nos. 5,261,291 and 5,431,663.

FIGS. 1A to 1C and FIG. 1F schematically illustrate one arrangement ofan ultrasonic catheter 10 that can be used to treat a blood clot in thebrain resulting from an intracerebral hemorrhage (ICH) and/or anintraventricular hemorrhage (IVH). FIG. 1B shows an enlarged detail viewof a distal portion 12 of the catheter 10 and FIG. 1C illustrates anenlarged detail view of a proximal portion 14 of the catheter 10. In theillustrated arrangement, the ultrasonic catheter 10 generally includes amulti-component, elongate flexible tubular body 16 having a proximalregion 14 and a distal region 12. The tubular body 16 includes aflexible energy delivery section 18 located in the distal region 12.Within the distal region 12 are located a plurality of holes 20, throughwhich fluid may flow into or out of a central lumen 22 (FIG. 1F) thatextends through the catheter 10. Although the drainage holes 20 areshown as circular, the shape of the holes may be varied. For instance,the drainage holes may be oval, polygonal, or irregular. FIGS. 1G and 1Hillustrate modified embodiments of the catheter which include separatelumens for fluid delivery and for fluid evacuation.

The catheter 10 defines the hollow lumen 22 which allows for the freeflow of liquids between the drainage holes 20 and the proximal port 24.For instance, blood may flow from an area external to the ultrasoniccatheter through the drainage holes 20 and into the lumen 22. The bloodmay then flow proximally in the lumen 22 towards the proximal region 14of the ultrasonic catheter, where it may be collected via the drainagekit. In certain embodiments, any number of therapeutic compounds may beintroduced into the ultrasonic catheter through the proximal end 14. Thecompounds, which may be dissolved or suspended within a liquid carrier,may flow through the lumen 22 and towards the distal end 12 of theultrasonic catheter, ultimately exiting the catheter through drainageholes 20 and entering a treatment site.

In certain embodiments, negative pressure may be applied to the lumen 22of the catheter to facilitate the flow of blood from the drainage holes20 towards the proximal end 14. In other embodiments, no externalpressure is applied, and the conditions present at the treatment siteare sufficient to cause the blood to flow proximally through the lumen22. In some embodiments, a positive pressure may be applied to the lumen22 of the catheter 10 in order for therapeutic compounds or otherliquids to pass distally through the lumen 22 towards the drainage holes20. In other embodiments, no external pressure is applied, and theliquid is permitted to independently flow distally and exit the drainageports 20.

The tubular body 16 and other components of the catheter 10 can bemanufactured in accordance with a variety of techniques known to anordinarily skilled artisan. Suitable materials and dimensions can bereadily selected based on the natural and anatomical dimensions of thetreatment site and on the desired access site. In addition, the surfaceof the catheter 10 can be coated with an antimicrobial material, such assilver or a silver based compound. In certain embodiments, the cathetermay be biocompatible for use in the brain for up to 7 days, for up to 15days, up to 29 days, or for up to 35 days. In one arrangement, thecatheter can be coated with a hydrophilic material.

In some embodiments, the tubular body 16 can be between about 23 and 29centimeters in length. In certain arrangements, the lumen 22 has aminimum inner diameter of about 2 millimeters and the catheter body hasa maximum outer diameter of about 6 mm.

In one particular embodiment, the tubular body 16 has materialproperties similar to that of standard external ventricular drainage(EVD) catheters. For example, the tubular body can be formed ofradiopaque polyurethane or silicone, which can be provided withantimicrobial features. In such embodiments, the catheter 10 by itselfmay not have sufficient flexibility, hoop strength, kink resistance,rigidity and structural support to push the energy delivery section 18through an opening in the skull and then, in turn, the patient's braintissue to a treatment site (e.g., one of the ventricles). Accordingly,the catheter 10 can be used in combination with a stylet 26 (FIG. 1D),which can be positioned within the tubular body 10. In one embodiment,the device is configured to be compatible with Neuronaviagation systemsby easily accommodating the Neuronavigation system stylet. The stylet 26can provide additional kink resistance, rigidity and structural supportto the catheter 10 such that it can be advanced through the patients'brain tissue to the target site. In certain embodiments, the stylet 26can be configured to be used in combination with a standard image guidedEVD placement system. As described below, after placement, the stylet 26can then be removed to allow drainage through the tubular body 16. In amodified arrangement, the tubular body 16 can be reinforced by braiding,mesh or other constructions to provide increased kink resistance andability to be pushed with or without a stylet.

In one embodiment, the tubular body energy delivery section 18 cancomprise a material that is thinner than the material comprising thetubular body proximal region 14. In another exemplary embodiment, thetubular body energy delivery section 18 comprises a material that has agreater acoustic transparency than the material comprising the tubularbody proximal region 14. In certain embodiments, the energy deliverysection 18 comprises the same material or a material of the samethickness as the proximal region 14.

FIG. 1C shows an enlarged detail view of the proximal portion 14 of theultrasonic catheter 10. The proximal portion 14 includes a connector 28.In the embodiment shown, the connector 28 comprises a series of annularrings 30 aligned in parallel. The connector 28 permits the catheter 10to be joined to a drainage kit. For example, in one arrangement, theconnector 28 is configured to connect to a standard EVD drainage kitthat can include an attachment fitting that slides over the connector 28or can include a buckle or joint that is fastened around connector 28.Specific length and configuration of the connector 28 can vary accordingto the needs of the particular application, and to facilitate connectionwith various drainage kits. Additionally, the number of annular rings 30may vary in certain embodiments.

In the illustrated arrangement of FIGS. 1A-D and 1F, the catheter 10 canbe use in combination with an inner core 32 (FIG. 1E) which can beinserted into the lumen 22 after the stylet 26 has been removed todeliver ultrasound energy to the target site. The core 32 can includeproximal hub 34 fitted on one end of the inner core 32 proximal region.One or more ultrasound radiating members 36 are positioned within adistal region of the core and are coupled by wires 38 to the proximalhub 34. In some embodiments, the inner core 32 can be inserted into thelumen 22 and/or along a side of the catheter 10. In yet anotherarrangement, the core 32 can be inserted into the lumen 22 with thedistal end including the ultrasound radiating members extending outsideone of the holes positioned on the distal region of the catheter 10.

In other embodiments, the catheter 10 can include separate lumens fordrainage and for drug delivery. FIGS. 1G and 1H show cross-sectionalviews of two embodiments of a catheter with multiple lumens. Withreference to FIG. 1G, a fluid-delivery lumen 23 is located within thewall of the catheter 10, between the outer surface and the inner lumen22, which may be used for fluid evacuation. In other embodiments, aplurality of fluid-delivery lumens 23 may be arranged within thecatheter 10. Although shown as substantially circular in cross-section,any number of shapes may be employed to provide for optimal fluid flowthrough the fluid-delivery lumen 23. With reference to FIG. 1H, aseparate fluid-delivery lumen 23 is located within a separate tuberunning longitudinally within the inner lumen 22. In certainembodiments, a plurality of fluid-delivery lumens 23 may be arrangedwithin inner lumen 22. The size of fluid-delivery lumen 23 may be smallenough so as to not interfere with the function of inner lumen 23 inevacuating fluid from the treatment site.

These separate lumens connect drainage and drug delivery holespositioned generally at the distal end of the catheter with drugdelivery and drainage ports positioned at the proximal end of thecatheter. In one embodiment, the device can include separate lumens forthe drug and drain delivery such that the holes and ports for drugdelivery and drainage are separated from each other. In someembodiments, the treatment zone (defined as the distance between thedistal most and proximal most ultrasound transducer) can be about 1 to 4cm. In other embodiments, the treatment zone may extend as far as 10 cm.The drug and drain ports can include luer type fittings. The ultrasoundtransducers can be positioned near or between the drain and drugdelivery holes.

FIGS. 2A-D are schematic illustrations of an ultrasonic catheteraccording to another embodiment. The catheter 10 contains componentssimilar to that shown in FIGS. 1A-C and FIG. 1F-H. However, in thisembodiment, includes wires 38 embedded within the wall of the tube. Aswill be explained below, the wires can activate and control ultrasonicradiating elements located within the distal region 12 of the catheter10. Additionally, the catheter 10 may include thermocouples formonitoring temperature of the treatment zone, the catheter, orsurrounding areas. In some embodiments, each ultrasound radiatingelement is associated with a temperature sensor that monitors thetemperature of the ultrasound radiating element. In other embodiments,the ultrasound radiating element itself is also a temperature sensor andcan provide temperature feedback. In certain embodiments, one or morepressure sensors are also positioned to monitor pressure of thetreatment site or of the liquid within the lumen of the catheter.

In the embodiment shown, the wires 38 are bundled and embedded withinthe wall of the tubular body 16. In other embodiments, the wires may notbe bundled, but may, for example, each be spaced apart from one another.Additionally, in certain embodiments the wires may not be embeddedwithin the wall of the tubular body 16, but may rather run within thelumen 22. The wires 38 may include protective and/or insulative coating.

The wires may be advantageously configured such that they can withstandtension applied to the catheter. For example, the wires may be able towithstand at least 3 pounds of tension. In other embodiments, the wiresmay be able to withstand at least 3.6 pounds, at least 4 pounds, or atleast 4.5 pounds of tension.

The wires may also be configured such that they increase the stiffnessof the tubular body 16 as little as possible. The flexibility of thetubular body 16 facilitates the introduction of the catheter 10 into thecranial cavity. It may therefore be advantageous to select wires thatonly minimally contribute to the stiffness of the catheter. The wireschosen may be between 30 and 48 gauge. In other embodiments, the wiresmay be between 33 and 45 gauge, between 36 and 42 gauge, or between 38and 40 gauge. The number of wires within the catheter is determined bythe number of elements and thermocouples in a particular device.

In certain embodiments, the drainage holes 20 include radii on theoutside of the holes, as can be seen in FIG. 2B. Applying a largerexternal radius to each drainage hole may improve the flow of blood intothe drainage holes 20 and through the lumen of the catheter and mayreduce damage to brain tissue during insertion and withdrawal. Althoughthe drainage holes 20 are depicted as arranged in regular rows, thepattern may vary considerably. The length of the region in which theholes are located may be between 2 and 4 cm. In certain embodiments, thelength may be between 2.5 and 3.5 cm, or the length may be about 3 cm.

In the embodiment shown, the annular rings 30 located within in theproximal region 14 of the catheter 10 may be connected to the wires 38.In certain embodiments, a wire may be soldered to each annular ring 30.An electrical contact may then be exposed on the outer diameter of theannular ring 30 to provide for an electrical connection to an individualwire. By virtue of this design, each wire, and therefore eachthermocouple or element, may be addressed independently. In alternativeembodiments, two or more wires may be soldered to an annular ring,thereby creating a single electrical connection. In other embodiments,the wires may meet electrical contacts at other points within thecatheter 10. Alternatively, the wires may pass through the wall of thetubular body 16 and connect directly to external apparatuses.

FIG. 3 is a schematic illustration of an ultrasonic catheter partiallyinserted into the brain. The catheter 10 may be positioned against theexternal surface of the skull, with the distal portion inserted throughbore 40. The bore 40 creates an access path through the skull 42, dura44, and into the brain tissue 46. Once in the brain tissue 46, excessblood resulting from hemorrhaging may be accepted into the drainageholes 20 located on the distal region of the catheter. Due to the angleof entry into the brain, the tubular body 16 of the catheter 10 isadvantageously kink resistant, in particular around a bend. Kinkresistance is advantageous at the distal region 12 of the catheter 10.As the catheter 10 is withdrawn from the brain tissue 46 and begins tostraighten, excess stiffness of the catheter can result in the distaltip migrating into the brain tissue 46. The presence of the drainageholes 20 contributes to the flexibility at the distal region 12 of thecatheter 10.

In one embodiment, the device can be placed using a tunneling techniquewhich involves pulling the device under the scalp away from the point ofentry in the brain to reduce the probability of catheter-initiatedinfections. In one embodiment, the catheter is made (at least partially)of a soft and pliant silicone material (and/or similar material) whichwill move with the brain matter during therapy without causing injury.

Dimensions of an ultrasonic catheter may vary according to differentembodiments. For example, the Wall Factor is defined as the ratio of theouter diameter of the tube to the wall thickness. The inventors havediscovered that a Wall Factor of 4 is useful in preventing kinking ofthe catheter. In particular, a Wall Factor of 4 may prevent kinking ofthe catheter around a 10 mm diameter bend, with the bend measuredthrough the centerline of the catheter. The area of the tubular body 16in which kink resistance is most advantageous is between 5 and 12 cmfrom the distal end of the device.

Various methods may be employed to impart kink resistance to thecatheter 10. For instance, the tubular body 16 may be reinforced withcoil to prevent kinking of the catheter around bends. In otherembodiments, the tubular body has a wall thickness that is chosen (inlight of the material) sufficient to prevent kinking as the catheter isplaced through a bend.

FIGS. 4A-B illustrates one arrangement of the ultrasonic radiatingelements 36. FIG. 4B is an enlarged detailed view of a cross-section ofthe ultrasonic catheter shown in FIG. 4A. As shown, in one arrangement,the ultrasonic radiating elements 36 can be disposed in the distalregion 12 of the ultrasonic catheter 10. In other embodiments,thermocouples, pressure sensors, or other elements may also be disposedwithin the distal region 12. The distal region 12 may be composed ofsilicone or other suitable material, designed with drainage holes 20 asdiscussed above. Ultrasonic radiating elements 36 may be embedded withinthe wall of the distal region 12, surrounded by the silicone or othermaterial. In addition to the ultrasonic radiating elements 36, thecatheter may include wiring embedded within the wall of the flexibletubular body, as discussed in more detail above with reference to FIGS.2A-2D. The ultrasonic radiating elements 36 can include connectivewiring, discussed in greater detail below. In various embodiments, theremay be as few as one and as many as 10 ultrasonic radiating elements 36can be embedded with the distal region 12 of the device. The elements 36can be equally spaced in the treatment zone. In other embodiments, theelements 36 can be grouped such that the spacing is not uniform betweenthem. In an exemplary embodiment, the catheter 10 includes twoultrasonic radiating elements 36. In this two-element configuration, theelements can be spaced apart approximately 1 cm axially, andapproximately 180 degrees circumferentially. In another embodiment, thecatheter 10 includes three ultrasonic radiating elements 36. In thisthree-element configuration, the elements 36 can be spaced approximately1 cm apart axially, and approximately 120 degrees apartcircumferentially. As will be apparent to the skilled artisan, variousother combinations of ultrasonic radiating elements are possible.

FIGS. 5A-B illustrates another arrangement of the distal region of anultrasonic catheter 10. FIG. 5B is an enlarged detail view of across-section of the ultrasonic catheter shown in FIG. 5A. In theconfiguration shown, two elements are spaced approximately 180 degreesapart circumferentially, and are equidistant from the distal tip of thecatheter 10. The catheter can include only two ultrasonic radiatingelements 36 in the distal region 12, or alternatively it may includefour, six, eight, or more, with each pair arranged in the configurationshown. In embodiments containing more than one pair, the pairs may bealigned axially. Alternatively, each pair may be rotated slightly withrespect to another pair of elements. In certain embodiments, each pairof radiating elements 36 are spaced apart axially approximately 1 cm.

Still referring to FIG. 5B, an epoxy housing 48 is shown, surrounded byan external layer of silicone 50. In the embodiment shown, theultrasonic radiating elements 36 are potted in the epoxy housing 48. Theepoxy may be flush with the outer diameter of silicone 50. The epoxyhousing 48 may have an axial length less than the length of the distalregion 12. In embodiments including multiple pairs of ultrasonicradiating elements 36, each pair of elements may be confined to aseparate epoxy housing 48. In one embodiment, the epoxy housing 48 mayhave an axial length of between 0.75 and 0.2 inches. In otherembodiments, the epoxy housing 48 may have an axial length of between0.1 and 0.15 inches, between 0.11 and 0.12 inches, or approximately0.115 inches.

FIGS. 6A-B show two embodiments of epoxy housings 48 in which anultrasonic radiating element 36 may be housed. Although the housingdepicted is made from epoxy, any suitable material may be used. Forinstance, the housing may be made from rubber, polyurethane, or anypolymer of suitable flexibility and stiffness. In embodiments employingepoxy, the housing may be formed by filling a polyimide sleeve withepoxy followed by curing.

In some embodiments, epoxy housings 48 may be embedded in the siliconelayer with the assistance of chemical adhesives. In other embodiments,the housings 48 may additionally contain structural designs to improvethe stability of the housing within the silicone. For instance, thehousing 48 shown in FIG. 6A contains a notch 52 which, when fitted witha complementary structure of a silicone layer, may improve the stabilityof the housing 48 within the silicone layer. Such structural designs maybe used in conjunction with or independently of chemical adhesives. FIG.6B shows another embodiment of an epoxy housing 48. In this embodiment,the raised ridge 54 is designed such that the top surface may lie flushwith a silicone layer that surrounds the epoxy housing 48. The presenceof ridge 54, when positioned with a complementary silicone layerstructure, may help to maintain the position of the housing, andtherefore of the ultrasonic radiating element, with respect to theultrasonic catheter.

FIGS. 7A-C show an ultrasonic catheter with a modified connector 28 thatcan be used in combination with the arrangements and embodimentsdescribed above. The catheter 10 includes flexible tubular body. Distalto the connector 28 is the proximal port 24, which is in communicationwith the lumen of the tubular body 16. In the embodiment shown, theproximal port 24 is coaxial with the lumen of the tubular body 16. Inuse, blood from the treatment site may enter the lumen through thedrainage holes 20 located on the distal region 12 of the catheter 10.Blood may then flow through the lumen and exit through proximal port 24into a drainage kit. In some embodiments, a negative pressure is appliedto the lumen of the catheter 10 to facilitate movement of the blood orother liquids at the treatment site proximally along the lumen and outthe proximal port 24. In other embodiments, no external pressure isapplied, and the blood or other liquid is permitted to flow from thetreatment site to the proximal port 24, unaided by external pressure. Incertain instances, the treatment site will possess relatively highpressure due to intracranial hemorrhaging. In such instances, thenatural pressure of the treatment site may cause blood or other liquidsto flow from the treatment site proximally along the lumen, and out theproximal port 24. Blood or other liquids may be drained at defined timeintervals or continuously throughout the treatment. By continuouslydraining fluid the clot, under compression, may move towards theultrasonic transducers for optimum ultrasound enhancement. Additionally,therapeutic agents may pass in the opposite direction. Such agents mayenter the proximal port 24, pass distally through the lumen, and exitthe catheter 10 through the drainage holes 20. In some embodiments, apositive pressure is applied to facilitate movement of the therapeuticagent or other liquid distally through the lumen and out the drainageholes 20. In other embodiments, no external pressure is applied, and theliquid is permitted to flow independently through the lumen. Therapeuticagents may be delivered in the form of a bolus within defined timeintervals or continuously throughout the treatment. In order to allowfor an exit path through the proximal port 24, the connector 28 isoriented at an angle with respect to the tubular body 16. In someembodiments, the connector lies at an angle between 10 and 90 degrees.In other embodiments, the connector 28 lies at an angle between 10 and60 degrees, between 12 and 45 degrees, between 20 and 30 degrees, orapproximately 22.5 degrees.

As described above with respect to other embodiments, the connector 28may be configured to provide electrical connections to the ultrasoundradiating elements. In the embodiments shown, however, the connector 28may lie at an angle with respect to the tubular body 16. In certainembodiments, a wire may be soldered to a contact point on the innerportion of connector 28. An electrical contact may then be exposed onthe outer surface of the connector 28 to provide for an electricalconnection to an individual wire. By virtue of this design, each wire,and therefore each thermocouple or element, may be addressedindependently. In alternative embodiments, two or more wires may besoldered to a single contact, thereby creating a single electricalconnection. In other embodiments, the wires may meet electrical contactsat other points within the catheter 10. Alternatively, the wires maypass through the wall of the tubular body 16 and connect directly toexternal apparatuses.

The catheter 10 may be advanced until distal region 12 reaches thedesired treatment site. For instance, the catheter 10 may be advancedthrough the cranial cavity until it is proximate to a blood clot.Therapeutic agents may then be delivered to the treatment site by thepath described above. For instance, thrombolytic agents may be deliveredto the treatment site, in order to dissolve the blood clot. In certainembodiments, ultrasonic energy may then be applied to the treatmentsite, as discussed above. Ultrasonic energy, alone or in combinationwith thrombolytic agents, may advantageously expedite dissolution of theblood clot. The ultrasonic energy may be applied continuously,periodically, sporadically, or otherwise. As the blood clot dissolves,excess blood may be drained from the treatment site through drainageholes 20. Excess blood entering the drainage holes 20 may pass throughthe lumen to the proximal port 24 and into a drainage kit or otherdisposal mechanism.

A modified embodiment of an ultrasonic catheter with a proximal port isshown in FIGS. 8A-B. In the embodiment shown, the proximal port 24 islocated on the flexible tubular body 16 and is in communication with thelumen of the tubular body 16. In this configuration, the proximal port24 is perpendicular to the axis of the tubular body 16, as opposed tothe configuration depicted in FIGS. 7A-C, in which the proximal port 24is coaxial with the tubular body 16. Positioning the proximal port 24 onthe wall of the tubular body 16 removes the need for the connector tolie at an angle with respect to the tubular body 16.

As discussed above, therapeutic agents may flow through proximal port24, distally through the lumen, and may exit the catheter 10 through thedrainage holes 20 in distal region 12. Additionally, blood or otherliquid may flow in the opposite direction, entering the catheter throughdrainage holes 20, flowing proximally through the lumen, and exiting thecatheter 10 through proximal port 24 and into a drainage kit or otherdisposal means. Ultrasonic energy may also be applied periodically,continuously, sporadically, or otherwise throughout the process asdesired. In certain embodiments, external pressure, negative orpositive, may be applied in order to facilitate movement of liquids fromthe proximal port 24 through the lumen and out drainage holes 20, or inthe opposite direction. In other embodiments, liquids are permitted toflow through the lumen, unaided by external pressure.

FIGS. 9A-F illustrate another arrangement for arranging the wires of anultrasonic catheter. This arrangement can be used with the embodimentsand arrangements described above. In this arrangement, a spiral grooveextrusion 56 provides structural support to the tubular body 16. Incertain embodiments, the groove extrusion 56 may be replaced by asimilar structure formed by molding or any other method. The spiralgroove design can provide improved kink resistance compared to a solidstructure. The spiral groove extrusion 56 may be formed of a variety ofdifferent materials. For example, in one arrangement, metallic ribbonscan be used because of their strength-to-weight ratios, fibrousmaterials (both synthetic and natural). In certain embodiments,stainless steel or tungsten alloys may be used to form the spiral grooveextrusion 56. In certain embodiments, more malleable metals and alloys,e.g. gold, platinum, palladium, rhodium, etc. may be used. A platinumalloy with a small percentage of tungsten may be preferred due to itsradiopacity. A sleeve 58 is arranged to slide over the spiral grooveextrusion 56. The material for sleeve 58 may be formed of almost anybiocompatible material, such as polyvinyl acetate or any biocompatibleplastic or metal alloy. Distal extrusion 60 can house ultrasonicelements as well as drainage holes 20. The distal extrusion 60 can beformed of materials such as those described above with respect to spiralgroove extrusion 56. Wires 38 are affixed to the distal extrusion 60 andconnected to thermocouple or ultrasound radiating elements. A distal tip62 is fitted to the end of distal extrusion 60.

FIG. 9C shows a cross-sectional view of the ultrasonic catheter shown inFIG. 9B. Outer diameter 64 may be approximately 0.2 inches. In otherembodiments, the outer diameter 64 may be approximately 0.213 inches.The inner diameter 66 may be approximately 0.1 inches. In otherembodiments, the inner diameter may be approximately 0.106 inches. Aswill be apparent, the dimensions of the inner and outer diameters willbe selected according to the application intended based on, e.g., thediameter of the access path through the skull, the treatment site, thevolume of therapeutic agent delivered, and anticipated volume of bloodto be drained.

In the embodiment shown, the distal extrusion 60 may contain a window 68in which an ultrasound radiating element may be affixed. In otherembodiments, multiple ultrasonic radiating elements, each with acorresponding window 68, may be employed. As discussed above, thenumber, orientation, and relation of the ultrasonic radiating elements36 may vary widely.

FIG. 9E shows a cross-sectional view of distal extrusion 60 shown inFIG. 9D. The drainage holes 20 are, in the embodiment shown,longitudinal gaps in the external surface of the distal extrusion 60. Ascan be seen in FIG. 9E, the distal extrusion 60 contains four drainageholes 20, each positioned approximately 90 degrees apartcircumferentially. In other embodiments, two or three longitudinaldrainage holes may be employed. In exemplary embodiments, five or morelongitudinal drainage holes may be used.

FIGS. 10A-D show another embodiment of an ultrasonic catheter. As withFIGS. 9A-F, a spiral groove extrusion 56 provides the structural supportto the flexible tubular body 16. Sleeve 58 is dimensioned to fit overthe spiral extrusion 56. In the embodiment shown, the distal extrusion60 has been excluded. Instead, the spiral extrusion 56 includes at itsdistal end drainage holes 20. Additionally, sleeve 58 also containsholes 70 designed to align with the drainage holes 20 of the spiralgroove extrusion 56. In some embodiments, the spiral extrusion 56 andsleeve 58 may be joined before drainage holes 20 are drilled throughboth layers. Wires 38 are connected to ultrasound radiating elements 36.In the embodiment shown, the ultrasound radiating elements 36 and wires38 are arranged to lie between the spiral extrusion 56 and the sleeve58. As discussed above, the wires may be arranged in various otherconfigurations. In certain embodiments, the wires may be arranged to liewithin the spiral groove.

FIG. 10C shows a cross-sectional view of the proximal region of theultrasonic catheter shown in FIG. 10B. The outer diameter 64 of theflexible tubular body 16 may be approximately 0.2 inches. In certainembodiments, the outer diameter 64 may be approximately 0.197 inches.The inner diameter 66 of the flexible tubular body 16 may beapproximately 0.01 inches. In certain embodiments, the inner diameter 66may be approximately 0.098 inches. As described above, the dimensions ofthe inner and outer diameters may vary based on the intendedapplication.

As can be seen in FIG. 10D, in certain embodiments the spiral groove maybecome straight at the distal region 12 of the catheter. In thisarrangement, the straightened region permits drainage holes 20 to bedrilled in an arrangement of rows. Additionally, ultrasonic radiatingelements 36 and wires 38 may be arranged to lie within the straightportion of the groove.

FIG. 11A-I show an ultrasonic catheter assembly according to oneembodiment, in which a coaxial ultrasonic core is introduced into aseparate external drain.

FIGS. 11A-C illustrate one embodiment of a drain 96. The distal portion98 of the drain 96 includes drainage holes 100. In a preferredembodiment, the drainage holes 100 may span approximately 3 cm along thedistal portion 98. In other embodiments, the drainage holes 100 may spanshorter or longer distances, as desired. The drain 96 comprises anelongate tubular body 102, and may include distance markers 104.Distance markers 104 may be, for instance, colored stripes that surroundthe drain. In other embodiments, the distance markers 104 may benotches, grooves, radiopaque material, or any other material orstructure that allows the regions to be visualized. The distance markers104 may be spaced apart at regular intervals, for instance, every 2 cm,5 cm, or other distance. In other embodiments they may be spaced ingradually increasing intervals, gradually decreasing intervals,irregularly, or in any other manner. In some embodiments, the distancebetween each marker will be written onto external surface of the drain.The presence of distance markers 104 may advantageously facilitatecareful placement of the drain at a treatment site. In modifiedembodiments, a suture wing may be positioned at about 6 inches along thelength of the catheter. Allowing a physician to visually observe thedistance that the drain is advanced may improve control and placementprecision.

The drain 96 includes a central lumen 106 which allows for the free flowof liquids from the drainage holes 100 towards the proximal portion 108of the drain. As will be discussed in more detail below, in certainembodiments, any number of therapeutic compounds may be passed throughthe lumen 106 and out the drainage holes 100, where they then enter atreatment site. The diameter of the lumen may be approximately 2.2 mm,with an approximate outer diameter of 4.4 mm. In other embodiments,these diameters may be larger or smaller, as desired. As will beapparent to one of skill in the art, the inner and outer diameters ofthe drain 96 will be chosen based on desired treatment site, fluid flowrate through the lumen, the material used to construct the drain, andthe size of the ultrasonic core or any other element intended to passtherethrough. In one arrangement, the drain may operate at a flow rateof approximately 20 ml per hour, at a pressure of 10 mmHg.

FIGS. 11D-E show one embodiment of an ultrasonic core 110. Theultrasonic core 110 comprises an elongate shaft 112 and hub 114.Ultrasonic elements 36 are positioned coaxially with the elongate shaft112. In certain embodiments, the ultrasonic core includes between oneand four ultrasonic elements 36. In other embodiments, five or moreultrasonic elements 36 may be included. The elongate shaft 112 isdimensioned so as to be removably received within drain 96. Accordingly,in certain embodiments, the outer diameter of the elongate shaft isapproximately 0.8 mm, and the length of the elongate shaft isapproximately 31 cm.

The hub 114 is attached to elongate shaft 112 through a tapered collar116. A proximal fluid port 118 is in fluid communication with the hub.Fluids, such as therapeutic drugs, may be injected down the core throughproximal fluid port 118 towards the treatment zone. Introducing fluidsin this manner may permit the use of a smaller bolus of therapeutic drugas compared to introducing fluids through the drain as discussed above.Alternatively, fluids may be injected into the lumen 106 of drain 96through use of a Tuohy-Borst adapter attached thereto. Injecting fluidsthrough the lumen 106 of the drain 96 may require lower injectionpressure, although a larger bolus of therapeutic drug may be necessary.In either configuration, the therapeutic drug ultimately flows out ofdrainage holes 100 located in the distal region 98 of drain 96.

FIGS. 11F-I illustrate the catheter assembly 120 in which ultrasoniccore 110 is inserted within lumen 106 of drain 96. In certainembodiments, the drain 96 may be advanced to the treatment site,followed by insertion of the ultrasonic core 110 within the drain. Forinstance, the drain may be tunneled under the scalp, through a bore inthe skull, and into the brain. Then the ultrasonic core 110 may beinserted into the drain 96, and advanced until the elongate shaft 112reaches the distal region 98 of drain 96.

Upon insertion, ultrasonic elements 36 may be positioned near thedrainage holes 100, allowing for the application of ultrasonic energy tothe treatment site. As can be seen in FIGS. 11H and 11I, the distal endof the elongate shaft 112 of ultrasonic core 110 may include one or moreultrasonic elements 36. When advanced into the distal region 98 of drain96, the ultrasonic radiating element 36 would be located within theregion containing drainage holes 100. As discussed in more detail above,application of ultrasonic energy to a treatment site may aid indissolution of a blood clot. Introduction of therapeutic drugs throughthe catheter assembly 120 and out drainage holes 110 may further aid inthis process. As the clot is dissolved, excess blood or other fluid maybe received within the drainage holes 100 and evacuated from thetreatment site.

With reference now to FIGS. 12A and 12B, in alternative embodiments twoseparate lumens may be included, one for fluid evacuation and one forfluid delivery. FIG. 12A shows a catheter In certain embodiments,continuous fluid flow may be possible. For example, application ofpositive pressure at the drug delivery port and simultaneous applicationof vacuum at the drainage port may provide for continuous removal oftoxic blood components. Alternatively, influx and efflux could beaccomplished separately and intermittently to allow drugs to have aworking dwell time. In certain embodiments, the catheter design couldspatially separate drainage holes from drug delivery holes and inletports, with the ultrasound transducers in between. The ultrasoundradiating radially may prevent influx from going directly to efflux.

FIG. 12A-C illustrate one embodiment of an ultrasonic element and corewire. The ultrasonic core wire 114 comprises locking apertures 116 andpad 118. When integrated within a completed ultrasonic core orultrasonic catheter, the ultrasonic core wire 114 may be embedded insilicone. The two locking apertures 116 allow for silicone to flowthrough the opening, thereby providing for a mechanical lock thatsecures the element into the silicone. The locking apertures need not becircular, but may be any shape that permits silicone to flowtherethrough to create a mechanical lock. Additionally, in certainembodiments there may be one locking aperture 116. In other embodiments,there may be two, three, four, or more locking apertures 116, asdesired. Ultrasonic transducers 120 are affixed to either side of pad118. RF wires 122 are then mounted to be in communication withultrasonic transducers 120. A polyimide shell 124 may be formed aroundthe assembly of the pad 118, ultrasonic transducers 120, and RF wires122, as shown in FIG. 12C. The polyimide shell may be oval-shape to aidin correct orientation of the ultrasonic element, and to minimize theuse of epoxy in manufacturing.

FIG. 13 illustrates an ultrasonic element suspended in a fluid-filledchamber. The fluid-filled chamber 126 is bounded circumferentially by apolyimide shell 124, with plugs 128 defining the ends of thefluid-filled chamber. Ultrasonic core wire 114 and RF wires 122penetrate one of the plugs 128 to enter the fluid-filled chamber 126. Afluid-tight seal is provided at the point of penetration to ensure thatthe chamber retains its fluid. Within the fluid-filled chamber 126 arethe ultrasonic transducers 120 affixed to the ultrasonic core wire 114and in communication with RF wires 122. This design may provide forseveral advantages over other configurations. For instance, pottingultrasonic elements in epoxy may lead to absorption of water by theepoxy, potentially causing delamination of an ultrasonic element fromthe potting material. Delamination of an element reduces the ability ofthe ultrasonic energy to be transferred from the ultrasonic element tothe surrounding tissue. Suspending an ultrasonic element within afluid-filled chamber may advantageously avoid this problem. Theultrasonic energy emitted by the ultrasonic elements transfers easily influid, and there is no risk of delamination. In addition, suspendingultrasonic elements within a fluid-filled chamber may advantageouslyreduce the number of components needed for an ultrasonic core, as wellas potentially reducing assembly time.

FIG. 14 schematically illustrates one embodiment of a feedback controlsystem 72 that can be used with the catheter 10. The feedback controlsystem 72 allows the temperature at each temperature sensor 76 to bemonitored and allows the output power of the energy source 78 to beadjusted accordingly. In some embodiments, each ultrasound radiatingelement 36 is associated with a temperature sensor 76 that monitors thetemperature of the ultrasound radiating element 36 and allows thefeedback control system 72 to control the power delivered to eachultrasound radiating element 36. In some embodiments, the ultrasoundradiating element 36 itself is also a temperature sensor 76 and canprovide temperature feedback to the feedback control system 72. Inaddition, the feedback control system 72 allows the pressure at eachpressure sensor 80 to be monitored and allows the output power of theenergy source 78 to be adjusted accordingly. A physician can, ifdesired, override the closed or open loop system.

In an exemplary embodiment, the feedback control system 72 includes anenergy source 78, power circuits 82 and a power calculation device 84that is coupled to the ultrasound radiating elements 36 and a pump 86. Atemperature measurement device 88 is coupled to the temperature sensors76 in the tubular body 16. A pressure measurement device 90 is coupledto the pressure sensors 80. A processing unit 94 is coupled to the powercalculation device 84, the power circuits 82 and a user interface anddisplay 92.

In an exemplary method of operation, the temperature at each temperaturesensor 76 is determined by the temperature measurement device 88. Theprocessing unit 94 receives each determined temperature from thetemperature measurement device 88. The determined temperature can thenbe displayed to the user at the user interface and display 92.

In an exemplary embodiment, the processing unit 94 includes logic forgenerating a temperature control signal. The temperature control signalis proportional to the difference between the measured temperature and adesired temperature. The desired temperature can be determined by theuser (as set at the user interface and display 92) or can be presetwithin the processing unit 94.

In such embodiments, the temperature control signal is received by thepower circuits 82. The power circuits 82 are configured to adjust thepower level, voltage, phase and/or current of the electrical energysupplied to the ultrasound radiating elements 36 from the energy source78. For example, when the temperature control signal is above aparticular level, the power supplied to a particular group of ultrasoundradiating elements 36 is reduced in response to that temperature controlsignal. Similarly, when the temperature control signal is below aparticular level, the power supplied to a particular group of ultrasoundradiating elements 36 is increased in response to that temperaturecontrol signal. After each power adjustment, the processing unit 94monitors the temperature sensors 76 and produces another temperaturecontrol signal which is received by the power circuits 82.

In an exemplary method of operation, the pressure at each pressuresensor 80 is determined by the pressure measurement device 90. Theprocessing unit 94 receives each determined pressure from the pressuremeasurement device 90. The determined pressure can then be displayed tothe user at the user interface and display 92.

In an exemplary embodiment, the processing unit 94 includes logic forgenerating a pressure control signal. The pressure control signal isproportional to the difference between the measured pressure and adesired pressure. The desired pressure can be determined by the user (asset at the user interface and display 92) or can be preset within theprocessing unit 94.

As noted above, it is generally desirable to provide low negativepressure to the lumen in order to reduce the risk of sucking solidmaterial, such as brain matter, into the lumen. Furthermore, becausereduction of intracranial pressure is often desirable in treating ICH,it is often desirable to deliver fluids with little pressuredifferential between the delivery pressure and the intracranial pressurearound the catheter. Accordingly, the processing unit 94 can beconfigured to monitor the pressure and modify or cease the delivery offluid and/or increase evacuation of fluid to the treatment site ifintracranial pressure increases beyond a specified limit.

In other embodiments, the pressure control signal is received by thepower circuits 82. The power circuits 82 are configured to adjust thepower level, voltage, phase and/or current of the electrical energysupplied to the pump 86 from the energy source 78. For example, when thepressure control signal is above a particular level, the power suppliedto a particular pump 86 is reduced in response to that pressure controlsignal. Similarly, when the pressure control signal is below aparticular level, the power supplied to a particular pump 86 isincreased in response to that pressure control signal. After each poweradjustment, the processing unit 94 monitors the pressure sensors 80 andproduces another pressure control signal which is received by the powercircuits 82.

In an exemplary embodiment, the processing unit 94 optionally includessafety control logic. The safety control logic detects when thetemperature at a temperature sensor 76 and/or the pressure at a pressuresensor 80 exceeds a safety threshold. In this case, the processing unit94 can be configured to provide a temperature control signal and/orpressure control signal which causes the power circuits 82 to stop thedelivery of energy from the energy source 78 to that particular group ofultrasound radiating elements 36 and/or that particular pump 86.

Consequently, each group of ultrasound radiating elements 36 can beidentically adjusted in certain embodiments. For example, in a modifiedembodiment, the power, voltage, phase, and/or current supplied to eachgroup of ultrasound radiating elements 36 is adjusted in response to thetemperature sensor 76 which indicates the highest temperature. Makingvoltage, phase and/or current adjustments in response to the temperaturesensed by the temperature sensor 76 indicating the highest temperaturecan reduce overheating of the treatment site.

The processing unit 94 can also be configured to receive a power signalfrom the power calculation device 84. The power signal can be used todetermine the power being received by each group of ultrasound radiatingelements 36 and/or pump 86. The determined power can then be displayedto the user on the user interface and display 92.

As described above, the feedback control system 72 can be configured tomaintain tissue adjacent to the energy delivery section 18 below adesired temperature. For example, in certain applications, tissue at thetreatment site is to have a temperature increase of less than or equalto approximately 6 degrees C. As described above, the ultrasoundradiating elements 36 can be electrically connected such that each groupof ultrasound radiating elements 36 generates an independent output. Incertain embodiments, the output from the power circuit maintains aselected energy for each group of ultrasound radiating elements 36 for aselected length of time.

The processing unit 94 can comprise a digital or analog controller, suchas a computer with software. In embodiments wherein the processing unit94 is a computer, the computer can include a central processing unit(“CPU”) coupled through a system bus. In such embodiments, the userinterface and display 92 can include a mouse, a keyboard, a disk drive,a display monitor, a nonvolatile memory system, and/or other computercomponents. In an exemplary embodiment, program memory and/or datamemory is also coupled to the bus.

In another embodiment, in lieu of the series of power adjustmentsdescribed above, a profile of the power to be delivered to each group ofultrasound radiating elements 36 can be incorporated into the processingunit 94, such that a preset amount of ultrasonic energy to be deliveredis pre-profiled. In such embodiments, the power delivered to each groupof ultrasound radiating elements 36 is provided according to the presetprofiles.

In an exemplary embodiment, the ultrasound radiating elements areoperated in a pulsed mode. For example, in one embodiment, the timeaverage power supplied to the ultrasound radiating elements is betweenabout 0.1 watts and about 2 watts. In another embodiment, the timeaverage power supplied to the ultrasound radiating elements is betweenabout 0.5 watts and about 1.5 watts. In yet another embodiment, the timeaverage power supplied to the ultrasound radiating elements isapproximately 0.6 watts or approximately 1.2 watts. In an exemplaryembodiment, the duty cycle is between about 1% and about 50%. In anotherembodiment, the duty cycle is between about 5% and about 25%. In yetanother embodiment, the duty cycles is approximately 7.5% orapproximately 15%. In an exemplary embodiment, the pulse averaged poweris between about 0.1 watts and about 20 watts. In another embodiment,the pulse averaged power is between approximately 5 watts andapproximately 20 watts. In yet another embodiment, the pulse averagedpower is approximately 8 watts or approximately 16 watts. The amplitudeduring each pulse can be constant or varied.

In an exemplary embodiment, the pulse repetition rate is between about 5Hz and about 150 Hz. In another embodiment, the pulse repetition rate isbetween about 10 Hz and about 50 Hz. In yet another embodiment, thepulse repetition rate is approximately 30 Hz. In an exemplaryembodiment, the pulse duration is between about 1 millisecond and about50 milliseconds. In another embodiment, the pulse duration is betweenabout 1 millisecond and about 25 milliseconds. In yet anotherembodiment, the pulse duration is approximately 2.5 milliseconds orapproximately 5 milliseconds.

For example, in one particular embodiment, the ultrasound radiatingelements are operated at an average power of approximately 0.6 watts, aduty cycle of approximately 7.5%, a pulse repetition rate ofapproximately 30 Hz, a pulse average electrical power of approximately 8watts and a pulse duration of approximately 2.5 milliseconds.

In an exemplary embodiment, the ultrasound radiating element used withthe electrical parameters described herein has an acoustic efficiencygreater than approximately 50%. In another embodiment, the ultrasoundradiating element used with the electrical parameters described hereinhas an acoustic efficiency greater than approximately 75%. As describedherein, the ultrasound radiating elements can be formed in a variety ofshapes, such as, cylindrical (solid or hollow), flat, bar, triangular,and the like. In an exemplary embodiment, the length of the ultrasoundradiating element is between about 0.1 cm and about 0.5 cm, and thethickness or diameter of the ultrasound radiating element is betweenabout 0.02 cm and about 0.2 cm.

With reference now to FIG. 15, in one embodiment of a treatmentprotocol, patients can be taken to an operating room and placed undergeneral anesthesia for ultrasound and drainage catheter insertion.Patients can be registered using electromagnetic (EM) stealth, based onCT parameters for stereotactic placement of catheters using theMedtronic EM Stealth navigation system. However, as described above, inmodified embodiments, other navigation techniques and tools could beused. Using such navigation systems, an entry point for the burr holeand target point in the hemorrhage for the catheter tips can be chosen.In some embodiments, the burr-hole can be located for an occipitalapproach if the patient has an intraventricular hemorrhage. In someembodiments, the burr-hole can be located for a more frontal approach ifthe patient has an intracerebral hemorrhage located in the frontalportion of the brain. It should be appreciated that the location of theburr-hole or drill hole can be selected to reduce the path lengthbetween the blood clot and the hole in the patient's skull. In addition,it may be desirable in some cases to approach the blood clot from anangle that avoids certain portions of the brain.

In the illustrated embodiment, a Stealth guidance system (or otherguidance system or technique) can used to place a 12 French peel-awayintroducer through the burr hole into the desired location in thehemorrhage, to accommodate placement of the ultrasonic catheter 10. Inmodified arrangements, a different size and/or type of introducer couldbe used and/or the ultrasonic catheter can be inserted without anintroducer.

As shown in FIG. 15, the catheter 10 can be with the peel awayintroducer and the position confirmed by neuro-navigation or othernavigation technique. In one embodiment, the two catheters can then betunneled out through a separate stab wound in the skin and secured tothe patient. A portable CT scan can be done at the completion of theprocedure to confirm acceptable catheter placement. In one embodiment,the distal tip of the ultrasonic catheter 10 is generally positionedlong the longitudinal center (measured along the axis of the catheter)of the hemorrhage. As described above, in other embodiments, anultrasonic core can be place through a lumen in the catheter (see e.g.,FIGS. 1A-F). In other embodiments, the ultrasonic catheter can be placedalong side the catheter.

In one embodiment of use, patients with ICH or IVH can be treated afterthe CT scans to confirm no active bleeding and expansion of thehematoma. In one embodiment, such scans can be obtained approximately 3hours after catheter placement but before treatment had begun withultrasound and thrombolytic. In some embodiments, the treatment mayinclude injecting a thrombolytic drug into the hemorrhage through thecatheter. The catheter is then flushed and clamped for about 1 hour withthe drainage close and then opened to closed drainage at 10 cm below thelesion thus allowing the full dose of the thrombolytic drug to bedelivered into the clot. In one embodiment of use, patients withintraventricular hemorrhages, 1 mg of rt-PA can be injected and 0.3 mgrt-PA can be injected in patients with intraparenchymal hemorrhages.

In one embodiment of use, following about 1 hour of drug treatment, theclosed drainage can be opened below the lesion. The injections can berepeated about every 8 hours (e.g., at about 8 hours and about 16 hoursfrom the time of the initial injection) for a total of 3 doses over aperiod of about 24 hours. Computer Tomography (CT) imaging can beperformed at appropriate time during the treatment to determined rate oflysis and to monitor the progress of clot lysis. The drainage may alsobe evaluated by performing a CT. The ultrasound remains operating allthe time during the treatment, and may be turned off only during the CTimaging for the least possible length of time. Thus, in someembodiments, the ultrasound may be turned on at the time of the initialinjection and delivered continuously at the catheter tip for up to about24 hours.

Ultrasound energy can be delivered for a duration sufficient to enableadequate drug distribution in and/or around the blood clot. This can beaccomplished by either intermittent or continuous delivery of ultrasoundenergy. For example, ultrasound energy can be delivered for a set timeperiod to adequately distribute the drug to the blood clot, and thenturned off to allow the drug to act on the blood clot. Alternatively,ultrasound energy can be delivered substantially continuously after thedrug has been delivered to the blood clot to continuously redistributethe drug into the blood clot as the blood clot is successfully lysed. Inaddition, ultrasound energy can be delivered intermittently to reduceheating. Also, as described in U.S. application Ser. No. 11/971,172,filed Jan. 8, 2008, which is hereby incorporated by reference herein inits entirety, the power parameters controlling the delivery ofultrasound energy can be randomized or varied according to complexnon-linear algorithms in order to enhance the efficacy of the ultrasoundtreatment.

Drug delivery can be controlled by monitoring, for example, lysisbyproducts such as D-dimer in the effluent evacuated from the bloodclot. A high and/or increasing concentration of D-dimer in the effluentcan indicate that lysis of the blood clot is proceeding adequately, andtherefore drug delivery can be maintained, reduced or stopped. A low ordecreasing concentration of D-dimer in the effluent can indicate thatlysis of the blood clot is inadequate or slowing or that the clot isnearly dissolved, and therefore drug delivery can be increased if theclot is not nearly dissolved, and reduced or stopped if lysis is almostcomplete. Alternatively, lytic concentration can be monitored todetermine whether more drug should be delivered and whether lysis iscomplete. In some embodiments, as lysis of the blood clot proceeds,lytic is freed from the lysed clot, thereby increasing the concentrationof lytic in the effluent. Therefore, increased lytic concentration cancorrelate to lysis completion. One way of determining the concentrationof lytic and/or D-dimer in the effluent is to measure the color of theeffluent that is evacuated from the blood clot. The redder the effluent,the greater the concentration of lytic and/or D-dimer in the effluent.

In some embodiments, neuroprotective drugs or agents that assist in thefunctional recovery and/or the reduction of cell and tissue damage inthe brain can also be delivered to the brain and blood clot with themethods and apparatus described above. These neuroprotective drugs oragents can be delivered before, with, or after the delivery of thethrombolytic drugs. Delivery of these drugs using the methods andapparatus described above is particularly useful where the drug deliverythrough the blood brain barrier is enhanced with ultrasound treatment,or where ultrasound enhances cell penetration by the drug, or where thedrug is sonodynamic.

Another embodiment of an ultrasonic catheter is shown in FIGS. 16A-E.Similar to the embodiments described above with respect to FIGS. 2A-D,the catheter includes wires 38 embedded within the wall of the tubularbody 16. The wires 38 are connected to and may control ultrasonicradiating elements 36 located within the distal region 12 of thecatheter 10. The wires extend from the proximal end of the tubular body16. In certain embodiments, the wires extend more than six inches fromthe proximal end, so as to facilitate electrical connection withexternal devices. Drainage holes 20 are positioned in the distal region12 of the catheter 10, near the ultrasonic radiating elements 36. Inother embodiments, thermocouples, pressure sensors, or other elementsmay also be disposed within the distal region 12. The distal region 12may be composed of silicone or other suitable material, designed withdrainage holes 20 as discussed above. Ultrasonic radiating elements 36may be embedded within the wall of the distal region 12, surrounded bythe silicone or other material. In various embodiments, there may be asfew as one and as many as 10 ultrasonic radiating elements 36 can beembedded with the distal region 12 of the device. The elements 36 can beequally spaced in the treatment zone. In other embodiments, the elements36 can be grouped such that the spacing is not uniform between them. Inan exemplary embodiment illustrated in FIGS. 16B-D, the catheter 10includes four ultrasonic radiating elements 36. In this four-elementconfiguration, the elements can be spaced apart as pairs, with each pairlocated at a similar longitudinal position, but separated by 180 degreescircumferentially. The pairs of offset from one another both by 90degrees circumferentially and by a longitudinal distance along thelength of the catheter 10. As will be apparent to the skilled artisan,various other combinations of ultrasonic radiating elements arepossible.

While the foregoing detailed description has set forth several exemplaryembodiments of the apparatus and methods of the present invention, itshould be understood that the above description is illustrative only andis not limiting of the disclosed invention. It will be appreciated thatthe specific dimensions and configurations disclosed can differ fromthose described above, and that the methods described can be used withinany biological conduit within the body.

What is claimed is:
 1. An ultrasound catheter for treatment of a bloodclot resulting from an intracranial hemorrhage comprising: an elongatetubular body having a distal portion and a proximal portion, theelongate tubular body comprising an inner surface defining a lumen andan outer surface; a plurality of ultrasound radiating elementspositioned in the distal portion of the elongate tubular body betweenthe inner and outer surfaces of the tubular body; a surface configuredto form an electrical connection on the proximal portion of the tubularbody comprising annular rings in electrical connection with theplurality of radiating elements and a proximal port located on theproximal portion of the tubular body, the proximal port adjacent anddistal to the electrical connection, wherein the lumen includes aplurality of ports on the distal portion of the elongate tubular bodyconfigured to allow fluid to flow therethrough, wherein the proximalport opens on an outer surface of the elongate tubular body and isperpendicular to a longitudinal axis of the elongate tubular body; and astylet configured to be received within the lumen.
 2. The catheter ofclaim 1, wherein wires connect the electrical connection to theultrasound radiating elements in the elongate tubular body, wherein thewires are embedded within the elongate tubular body.
 3. The catheter ofclaim 1, further comprising a proximal port co-linear with the lumen. 4.The catheter of claim 1, wherein the ultrasound radiating elements arepotted in epoxy.
 5. The catheter of claim 1, wherein the ultrasoundradiating elements are suspended in a fluid.
 6. The catheter of claim 1,wherein the ultrasound radiating elements are positioned within a windowon the outer surface of the elongate tubular body.
 7. The catheter ofclaim 1, wherein the ultrasound radiating elements are positioned in thedistal portion of the elongate tubular body.
 8. The catheter of claim 1,wherein the elongate tubular body comprises a metal extrusion surroundedby a sleeve.
 9. The catheter of claim 8, wherein elongate tubular bodyfurther comprises a distal extrusion configured to be affixed to themetal extrusion, wherein the distal extrusion houses the ultrasoundradiating elements.
 10. The catheter of claim 8, wherein, the metalextrusion includes the distal portion containing the plurality of ports.11. The catheter of claim 8, wherein the extrusion is a spiralextrusion.
 12. The catheter of claim 1, wherein the ports are circular.13. The catheter of claim 1, wherein the ports comprise longitudinalopenings in the distal portion of the elongate tubular body.
 14. Thecatheter of claim 1, further comprising distance markers on the elongatetubular body.
 15. An ultrasound catheter comprising: an elongate tubularbody having a distal portion and a proximal portion, the elongatetubular body comprising walls defining a first drainage lumen within theelongate tubular body and a delivery lumen within the elongate tubularbody; wherein the elongate tubular body does not have sufficient hoopstrength, kink resistance, rigidity, and structural support to be pushedthrough an opening in a skull and into brain tissue; wherein thedrainage lumen includes a plurality of drainage ports on the distalportion of the elongate tubular body configured to allow fluid to flowtherethrough; wherein the delivery lumen includes a plurality ofdelivery ports on the distal portion of the elongate tubular bodyconfigured to allow fluid to flow therethrough; a plurality ofultrasound radiating elements positioned within, the walls of theelongate tubular body, wherein the ultrasound radiating elements arepiezoelectric ceramic oscillators; a surface configured to form anelectrical connection on the proximal portion of the elongate tubularbody and a proximal port located adjacent and distal to the electricalconnection, wherein the proximal port opens on an outer surface of theelongate tubular body in the proximal portion, wherein the proximal portis perpendicular to a longitudinal axis of the elongate tubular body;and a stylet configured to be received within the drainage lumen. 16.The ultrasound catheter of claim 15, wherein the elongate tubular bodyis formed in part from silicone.
 17. The ultrasound catheter of claim15, wherein the elongate tubular body has material properties same asthat of standard external ventricular drainage (EVD) catheter.
 18. Thecatheter of claim 1, wherein the elongate tubular body has materialproperties the same as that of standard external ventricular drainage(EVD) catheter, wherein the elongate tubular body does not havesufficient hoop strength, kink resistance, rigidity, and structuralsupport to be pushed through an opening in a skull and into braintissue.
 19. The catheter of claim 1, wherein the electrical connectionis located at an angle with respect to the elongate tubular body. 20.The catheter of claim 19, wherein the angle ranges between 10 and 60degrees.
 21. The catheter of claim 19, wherein the angle ranges between12 and 45 degrees.
 22. The catheter of claim 19, wherein the angle is22.5 degrees.